METACARTIN

Constituent of striated muscle and liver.

It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.

For treatment of primary systemic carnitine deficiency, a genetic impairment of normal biosynthesis or utilization of levocarnitine from dietary sources, or for the treatment of secondary carnitine deficiency resulting from an inborn error of metabolism such as glutaric aciduria II, methyl malonic aciduria, propionic acidemia, and medium chain fatty acylCoA dehydrogenase deficiency.

Used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.

Parenteral levocarnitine is indicated for the prevention and treatment of carnitine deficiency in patients with end-stage renal disease.

Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane.

It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations.

Lack of carnitine can lead to liver, heart, and muscle problems.

Carnitine deficiency is defined biochemically as abnormally low plasma concentrations of free carnitine, less than 20 µmol/L at one week post term and may be associated with low tissue and/or urine concentrations.

Further, this condition may be associated with a plasma concentration ratio of acylcarnitine/levocarnitine greater than 0.4 or abnormally elevated concentrations of acylcarnitine in the urine.

Only the

L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism.

The "vitamin BT" form actually contains D,L-carnitine, which competitively inhibits levocarnitine and can cause deficiency.

Levocarnitine can be used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias.

Levocarnitine can be synthesised within the body from the amino acids lysine or methionine.

C (ascorbic acid) is essential to the synthesis of carnitine.

Levocarnitine is a carrier molecule in the transport of long chain fatty acids across the inner mitochondrial membrane.

It also exports acyl groups from subcellular organelles and from cells to urine before they accumulate to toxic concentrations.

Only the

L isomer of carnitine (sometimes called vitamin BT) affects lipid metabolism.

Levocarnitine is handled by several proteins in different pathways including carnitine transporters, carnitine translocases, carnitine acetyltransferases and carnitine palmitoyltransferases.

O-palmitoyltransferase 1, muscle isoform activator Humans U Xanthine dehydrogenase/oxidase Not Available Humans U Liver carboxylesterase 1 Not Available Humans U Myeloperoxidase Not Available Humans U Carnitine O-palmitoyltransferase 1, liver isoform activator Humans U Solute carrier family 22 member 4 Not Available Humans U Organic cation/carnitine transporter 2 Not Available Humans U Carnitine O-acetyltransferase Not Available Humans U Mitochondrial basic amino acids transporter Not Available Humans U Mitochondrial carnitine/acylcarnitine carrier protein Not Available Humans U Peroxisomal carnitine O-octanoyltransferase Not Available Humans U Carnitine O-palmitoyltransferase 2, mitochondrial Not Available Humans.

Absolute bioavailability is 15% (tablets or solution).

Time to maximum plasma concentration was found to be 3.3 hours.

The steady state volume of distribution (Vss) of an Intravenous administered dose, above endogenous baseline levels, was calculated to be 29.0 +/.

• 7.1 L.

However this value is predicted to be an underestimate of the true Vss.

After oral administration

L-carnitine which is unabsorbed is metabolized in the gastrointestinal tract by bacterial microflora.

Major metabolites include trimethylamine

N-oxide and -gamma-butyrobetaine.

Hover over products below to view reaction partners Levocarnitine Trimethylamine N-oxide -gamma-Butyrobetaine.

Following a single intravenous dose, 73.1 +/.

• 16% of the dose was excreted in the urine during the 0-24 hour interval.

Post administration of oral carnitine supplements, in addition to a high carnitine diet, 58-65% of the administered radioactive dose was recovered from urine and feces in 5-11 days.

hours (elimination) following a single intravenous dose.

Total body clearance was found to be a mean of 4 L/h.

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8 g/kg (mouse, oral).

Adverse effects include hypertension, fever, tachycardia and seizures.

Serious hypersensitivity reactions, including rash, urticaria, and facial edema have been reported with oral levocarnitine.

Other serious hypersensitivity reactions, including anaphylaxis, laryngeal edema, and bronchospasm have been reported following intravenous levocarnitine administration, mostly in patients with end-stage renal disease undergoing dialysis.

Discontinue use of levocarnitine and instruct patients to seek medical attention if they experience symptoms suggestive of a hypersensitivity reaction.

None known.

For oral use only.

Not for parenteral use.

The recommended dosage of levocarnitine is to 3 g/day for a 50 kg subject, which is equivalent to to 30 mL/day of levocarnitine oral solution.

Higher doses should be administered only with caution and only where clinical and biochemical considerations make it seem likely that higher doses will be of benefit.

Dosage should start at 1 g/day (10 mL/day), and be increased slowly while assessing tolerance and therapeutic response.

Monitoring should include periodic blood chemistries, vital signs, plasma carnitine concentrations, and overall clinical condition.

Infants and children

The recommended dosage of levocarnitine is to 100 mg/kg/day which is equivalent to 0.5 mL/kg/day levocarnitine oral solution.

Dosage should start at 50 mg/kg/day, and be increased slowly to a maximum of 3 g/day (30 mL/day) while assessing tolerance and therapeutic response.

Levocarnitine oral solution may be consumed alone or dissolved in drink or other liquid food.

Doses should be spaced evenly throughout the day (every three or four hours) preferably during or following meals and should be consumed slowly in order to maximize tolerance.

Levocarnitine oral solution, USP is a clear colorless solution with cherry flavor, supplied in 118 mL (4 fl. oz). plastic containers (NDC 52817-830-04).

Store at controlled room temperature 15º to 30 ºC (59º to 86º F) .

Reproductive studies have been performed in rats and rabbits at doses up to 3.8 times the human dose on the basis of surface area and have revealed no evidence of impaired fertility or harm to the fetus due to levocarnitine.

There are, however, no adequate and well-controlled studies in pregnant women.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Levocarnitine supplementation in nursing mothers has not been specifically studied.

Studies in dairy cows indicate that the concentration of levocarnitine in milk is increased following exogenous administration of levocarnitine.

In nursing mothers receiving levocarnitine, any risks to the child of excess carnitine intake need to be weighed against the benefits of levocarnitine supplementation to the mother.

Consideration may be given to discontinuation of nursing or of levocarnitine treatment.